异基因造血细胞移植前使用I-阿帕米司他单抗对比传统治疗方案治疗复发/难治性急性髓系白血病的随机III期SIERRA试验
Randomized Phase III SIERRA Trial of I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML.
作者信息
Gyurkocza Boglarka, Nath Rajneesh, Seropian Stuart, Choe Hannah, Litzow Mark R, Abboud Camille, Koshy Nebu, Stiff Patrick, Tomlinson Benjamin, Abhyankar Sunil, Foran James, Hari Parameswaran, Chen George, Al-Kadhimi Zaid, Kebriaei Partow, Sabloff Mitchell, Orozco Johnnie J, Jamieson Katarzyna, Silverman Margarida, Van Besien Koen, Schuster Michael, Law Arjun Datt, Larkin Karilyn, Pandit-Taskar Neeta, Rowley Scott D, Munshi Pashna, Cook Rachel, Levy Moshe Y, Lazarus Hillard M, Sandmaier Brenda M, Pagel John M, Reddy Vijay, MacDougall James, McNamara Kathleen, Spross Jennifer, Haeuber Elaina, Vusirikala Madhuri, Nahar Akash, Desai Avinash, Giralt Sergio
机构信息
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, NY.
Banner MD Anderson Cancer Center, Gilbert, AZ.
出版信息
J Clin Oncol. 2025 Jan 10;43(2):201-213. doi: 10.1200/JCO.23.02018. Epub 2024 Sep 19.
PURPOSE
Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate I-apamistamab with conventional care.
METHODS
SIERRA (ClinicalTrials.gov identifier: NCT02665065) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an I-apamistamab-led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population.
RESULTS
The ITT population included 153 patients (I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the I-apamistamab and conventional care groups, respectively.
CONCLUSION
The I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. I-apamistamab was well tolerated and could address an unmet need in this population.
目的
复发或难治性急性髓系白血病（RR AML）老年患者若不进行异基因造血细胞移植（alloHCT），预后不佳。SIERRA研究比较了一种包含抗CD45放射性偶联物I-阿帕米司他单抗的靶向移植前方案与传统治疗。
方法
SIERRA（ClinicalTrials.gov标识符：NCT02665065）是一项III期开放标签试验。年龄≥55岁的活动性RR AML患者按1:1随机分配至alloHCT前接受以I-阿帕米司他单抗为主的方案或传统治疗，若初始获得完全缓解（CR）/血小板未完全恢复的CR（CRp），则后续接受alloHCT。I-阿帕米司他单抗组在alloHCT后28 - 56天评估初始反应，挽救化疗开始后28 - 42天评估传统治疗组；未达到CR/CRp或AML进展的患者可交叉接受I-阿帕米司他单抗治疗，随后进行alloHCT。主要终点是初始CR/CRp后持续180天的持久完全缓解（dCR）。次要终点是总生存期（OS）和无事件生存期（EFS），在意向性治疗（ITT）人群中分层评估。
结果
ITT人群包括153例患者（I-阿帕米司他单抗组[n = 76]；传统治疗组[n = 77]）。总计，77例传统治疗组患者中有44例交叉，40/77（52%）接受了I-阿帕米司他单抗和alloHCT，6例患者（13.6%）实现dCR。在ITT人群中，I-阿帕米司他单抗组的dCR率显著高于传统治疗组（17.1%[95%CI，9.4至27.5]），传统治疗组为0%[95%CI，0至4.7]；P <.0001）。OS风险比（HR）为0.99（95%CI，0.70至1.41；P =.96），EFS HR为0.23（95%CI，0.15至0.34），HR <1有利于I-阿帕米司他单抗。I-阿帕米司他单抗组和传统治疗组分别有59.7%和59.2%发生≥3级治疗相关不良事件。
结论
在RR AML老年患者中，以I-阿帕米司他单抗为主的方案与高于传统治疗的dCR率相关。I-阿帕米司他单抗耐受性良好，可满足该人群未满足的需求。
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